Regulation of brain fluid homeostasis by dynamic aquaporin-4 subcellular relocalisation

About the Project

Details of the Project

Background:

Aquaporins facilitate passive, bidirectional water transport in all cells and tissues. In the brain and spinal cord, aquaporin-4 facilitates the exchange of water across the blood-spinal cord and blood-brain barriers, controlling cell volume, extracellular space volume and astrocyte migration. Recently, we have demonstrated that aquaporin-4 localization is dynamically regulated at the subcellular level, affecting membrane water permeability. In animal models of ageing, stroke, traumatic injury and sleep disruption, all risk factors for neurodegeneration, both glymphatic function and aquaporin-4 perivascular localization are reduced. Brain and spinal cord oedema are caused by the influx of water through aquaporin-4 following insults such as traumatic injury, stroke or cancer. We have demonstrated that reducing dynamic subcellular relocalization of aquaporin-4 to the blood-spinal cord or blood-brain barriers reduces oedema and accelerates functional recovery in rodent injury models. Targeting dynamic aquaporin-4 subcellular relocalization provides a novel approach to modulating aquaporin-4 function for clinical benefit.

Objective:

The aim of this PhD project is to understand how aquaporin-4 localization is regulated in health and disease using in vitro and/or in vivo methods. We will use a suite of cutting edge biochemical and biophysical approaches to characterize this regulation.

The long-term impacts of this project will be the identification of a mechanistic framework to understand the fundamental physiological process of brain water homeostasis and the use of this knowledge to prevent brain swelling and neurodegeneration, contributing to an urgent and unmet clinical need for new effective medicines.

Key Papers:

Salman MM et al. Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis, Brain, 2022, 145, 64-75 (Featured on the front cover).

Salman MM, Kitchen P, Yool AJ and Bill RM: Recent breakthroughs and future directions in drugging aquaporins, Trends Pharmacol Sci, 2022, 43,30-42 (Featured on the front cover).

Kitchen P et al.: Targeting aquaporin-4 subcellular localization to treat central nervous system edema, Cell, 2020, 181, 784-799.

Overseas Applicants

Overseas applicants may apply for this studentship but will need to pay the difference between the ‘Home’ and the ‘Overseas’ tuition fees. Currently the difference between ‘Home’ and the ‘Overseas’ tuition fees is £17,712 for 2026/7. As part of the application, you will be required to confirm that you will provide this additional funding. Please indicate this on the application form in the funding section. This project has associated consumables costs which should be discussed with the supervisor in the first instance and before applying. The supervisor can be contacted at p.kitchen1@aston.ac.uk. When applying, please upload copies of your discussions with the supervisor as confirmation.

Location

This position will be based on the Aston Campus in Birmingham, UK. The successful candidate will need to be located within a reasonable distance of the campus, and will be expected to visit in person regularly.

Person Specification

Candidates should have been awarded, or expect to achieve, EITHER:

a] a First or Upper Second Class award in their undergraduate degree, in a relevant subject.

OR

b] a First or Upper Second Class award in their undergraduate degree, and a Merit or Distinction in a Masters degree, both in a relevant subject.

Qualifications from overseas institutions will be considered, but performance must be equivalent to that described above, and the University reserves the right to ascertain this equivalence according to its own criteria.

Contact information

For formal enquiries about this project contact Dr Philip Kitchen at p.kitchen1@aston.ac.uk

Submitting an application

We can only consider applications that are complete and have all supporting documents. Applications that do not provide all the relevant documents will be automatically rejected. Your application must include:

1. English language copies of the transcripts and certificates for all your higher education degrees, including any Bachelor degrees.
2. A Research Statement detailing your understanding of the research area, how you would approach the project, and a brief review of relevant literature. Be sure to use the title of the research project you are applying for. There is no set format or word count.
3. A personal statement which outlines any further information which you think is relevant to your application, such as your personal suitability for research, career aspirations, possible future research interests, and further description of relevant employment experience.
4. A Curriculum Vitae (Resume) which details your education and work history.
5. Two academic referees who can discuss your suitability for independent research. References must be on headed paper, signed and dated no more than 2 years old. At least one reference should be from your most recent University. You can submit your references at a later date if necessary.
6. Evidence that you meet the English Language requirements. If you do not currently meet the language requirements, you can submit this at a later stage.
7. A copy of your passport. Where relevant, include evidence of settled or pre-settled status.

Interviews

Interviews will be conducted online via Microsoft Teams. If you are shortlisted, you will be contacted directly with details of the interview.

Funding Notes

This project covers the Home tuition fees. Candidates who do not have Home status will be responsible for the difference in tuition fees. Currently the difference between ‘Home’ and the ‘Overseas’ tuition fees is £17,712 for 2026/7. This project has associated consumables costs which should be discussed with the supervisor in the first instance and before applying. The supervisor can be contacted at p.kitchen1@aston.ac.uk. When applying, please upload copies of your discussions with the supervisor as confirmation.